Choice of Antithyroid Medications in Hyperthyroidism

Hyperthyroidism is a condition where production of thyroid hormone is higher than normal, causing several symptoms and signs. This condition is usually due to autoimmune problem. Hyperthyroidism can be treated with medicines or with surgical procedures, depends on structural abnormality found in each case. Medicines can control the symptoms and signs of hypethyroidism, but cannot cure the basic problem causing this condition (i.e. autoimmune process).

Several medications which are used in pharmacological therapy against hyperthyroidism: radioiodine, thioureylenes (consists of carbimazole, propylthiouracil, and methimazole), and iodine.

1. Radioiodine

In USA, radioiodine is first-choice medicine for pharmacological therapy against hyperthyroidism. Radioiodine acts as original iodine, to compete against stable iodine to be incorporated into thyroglobulin. With dose of 5-15 millicurie (mCi), this medicine is given orally,  has half-life about 8 days, and gives maximum effect after 2 months. Due to its radiation effect, the patient treated with radioiodine will eventually develop hypothyroidism, but this condition can be cured with T4 replacement.
Radioiodine should not be used in children and pregnant women. This medicine is also used for treatment against thyroid cancer.

2. Carbimazole and Methimazole

Methimazole is an active form of carbimazole (this means, carbimazole is a prodrug). Carbimazole is more commonly used in Europe, meanwhile methimazole in USA. Methimazole inhibits two steps of thyroid hormone metabolism: iodination and coupling. This group of medicine decrease the output of thyroid hormones from the gland by inhibiting the iodination of tyrosyl residues in thyroglobulin. Methimazole and carbimazole also inhibits thyroperoxidase-catalyzed oxydation with competitive inhibition.
Adverse effects of methimazole are: neutropenia, agranulocytosis, sore throat, headache, and rashes.
Methimazole is used for many antithyroid population, including second and third-trimester of pregnancy. This kind of thioureylenes has been the first choice since risk of fatal fulminant hepatic failure of propylthiouracil.

3. Propylthiouracil (PTU, PROP)

Propylthiouracil is also a member of thioureylenes group, but besides those two effects against coupling and iodination steps, propylthiouracil also has effect against thyroid conversion (T4 to T3) in peripheral tissue.
Propylthiouracil is commonly used as antithyroid for pregnant women (first trimester) and women who are planning to be pregnant; due to its less antithyroid effect on fetus by those times. Other than those population, propylthiouracil use has been diminished due to risk of fulminant hepatic failure.

4. Iodine

Iodine itself is converted to be iodide (negative ion form). Iodide has a temporary effect to inhibit thyroid hormone release to the circulation. This medicine is useful especially in the setting of surgery, when the thyroid gland of a hyperthyroid patient needs to be resected. To reach its maximum effect, iodine should be given from 10-15 days before surgery. This process formerly called as lugolization (popular name in 1930s-1950s), due to iodine preparation used by that time (potassium iodide). Iodine is also used as therapy for thyroid (thyrotoxicosis) crisis. Be careful because iodine can trigger allergic reaction in some people.

Besides antithyroids, several supportive medicines are also necessary to be mentioned here, due to their relevancy against the same disease.

5. Propanolol

Propanolol has no effect at all on thyroid hormone metabolism, but this beta-blocker has useful effect in decreasing many signs and symptoms in hyperthyroidism; such as tachycardia/cardiac arrhythmia, tremor, agitation, and restlessness.

6. Glucocorticoids and guanethidine

Glucocorticoids (prednisolone or hydrocortisone) are used to alleviate exophthalmia, especially in severe form, in thyrotoxicosis. Guanethidine is also useful against ophthalmopathy in hyperthyroidism, i.e. to ameliorate the exophthalmos. It works as an antiadrenergic agent, to decrease the effect on sympathethically innervated smooth muscles that cause (upper) eyelid retraction.


References:
Rang & Dale's Pharmacology 7th edition, 2011: 414-415.